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Hyper‐reactive cloned mice generated by direct nuclear transfer of antigen‐specific CD 4 + T cells
Author(s) -
Kaminuma Osamu,
Katayama Kazufumi,
Inoue Kimiko,
Saeki Mayumi,
Nishimura Tomoe,
Kitamura Noriko,
Shimo Yusuke,
Tofukuji Soichi,
Ishida Satoru,
Ogonuki Narumi,
Kamimura Satoshi,
Oikawa Mami,
Katoh Shigeki,
Mori Akio,
Shichijo Michitaka,
Hiroi Takachika,
Ogura Atsuo
Publication year - 2017
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201643321
Subject(s) - t cell receptor , biology , antigen , immune system , t cell , t lymphocyte , immunology , microbiology and biotechnology
T‐cell receptor ( TCR )‐transgenic mice have been employed for evaluating antigen‐response mechanisms, but their non‐endogenous TCR might induce immune response differently than the physiologically expressed TCR . Nuclear transfer cloning produces animals that retain the donor genotype in all tissues including germline and immune systems. Taking advantage of this feature, we generated cloned mice that carry endogenously rearranged TCR genes from antigen‐specific CD 4 + T cells. We show that T cells of the cloned mice display distinct developmental pattern and antigen reactivity because of their endogenously pre‐rearranged TCR α ( rT α) and TCR β ( rT β) alleles. These alleles were transmitted to the offspring, allowing us to establish a set of mouse lines that show chronic‐type allergic phenotypes, that is, bronchial and nasal inflammation, upon local administrations of the corresponding antigens. Intriguingly, the existence of either rT α or rT β is sufficient to induce in vivo hypersensitivity. These cloned mice expressing intrinsic promoter‐regulated antigen‐specific TCR are a unique animal model with allergic predisposition for investigating CD 4 + T‐cell‐mediated pathogenesis and cellular commitment in immune diseases.